APOE4 carriers respond well to the DHA present in fish but do not respond as well to dietary supplements

“The benefits of dietary fish intake on cognitive function in APOE4 carriers have not been observed with DHA supplementation. Multiple studies demonstrate that supplementation with 2 g of DHA per day slows the progression of cognitive decline of AD in APOE4 noncarriers, but has no effect in APOE4 carriers (43, 44). In addition, the positive effects on brain neuropathology observed with high dietary fish intake in APOE4 carriers are not observed with DHA supplementation in APOE4 carriers (39). Furthermore, individuals with the APOE4 allele do not clear amyloid-β plaques after DHA supplementation, and APOE4 impairs DHA transport into the brain, suggesting a possible gene-diet interaction (45, 46).”

“APOE4 carriers respond well to the DHA present in fish but do not respond as well to dietary supplements.”

This is concerning because I have an APOE4. I started eating more fish. I already consume lots of sardines and I’ve added some other ocean fish as well. If I’m going to be eating much Seafood that’s higher in the food chain, I’ll have to add emerimide to keep from building up mercury. I’ll get some krill oil and eat a lot more ocean fish.



This concerns me as well. Unfortunately I’m APOE 4/4. Really a big worry in my life. I was taking huge doses of fish oil high in EPA and DHA but I’m thinking of stopping. Krill oil is so expensive it does not seem reasonable. Tinned fish doesn’t agree with me as I have issue with histamine intolerance. I’ve started eating a portion of frozen salmon everyday cooked mostly in the microwave for convenience.


On another note, you should look at the apoA1 hypothesis by NewAmsterdam Pharma.

canned cod liver, cheap, pretty tasty and floating in non oxidized fish oil


@Vulcan I carry a single allele of APOE4 too and am realizing I need to be more proactive. How do you obtain Emeramide? I looked it up and in the US it seems like a big production, due to its status as a “compassionate use” drug.

Ebselen also sounds like a good chelator but don’t know re: availability.

My APOE genotype is E3/E4. This quote from the paper seems important

“I suggest that APOE4 carriers respond to DHA from fish but not DHA supplements because fish contains DHA in phospholipid form, whereas supplements do not. This difference in form influences whether DHA is metabolized to nonesterified DHA (free DHA) or a specific phospholipid form called lysophosphatidylcholine DHA (DHA-lysoPC).”

Depending on your budget I think the following makes sense.

  1. Consume foods rich in DHA (and relatively low in mercury) such as Salmon Roe or buy a DHA supplement in phospholipid form (more expensive per mg than other supplements) such as this Omega-3 Phospholipids™ - Omega-3 Fish Oils

  2. Test your Omega 3 ratios before/after to track your changes Omega-3 Index Complete | OmegaQuant

According to Dr. Goodenow DHA needs to be converted in the body to DHA-Plasmalogen to be useful : Plasmalogens. Both aging and having the APOE4 genotypes slows down the body’s ability to convert DHA to DHA-Plasmalogen. All animals (including seafood sourced for DHA) contain some of the DHA as DHA-Plasmalogen and a fraction of it survives digestion intact : this might explain the higher benefits seen from DHA from seafood but not from DHA supplements. But since only a small fraction of DHA-Plamalogen survives digestion intact (the rest is broken down into DHA and Phospholipids), even with DHA from seafood, it is very hard with APOE4 (or old age) to get enough DHA-Plasmalogen.

The workaround, according to Dr. Goodenow, is to supplement with a synthetic precursor to DHA-Plasmalogen that is more able to survive digestion intact AND easiliy converted to DHA-Plasmalogen, even in aging humans or those with genetically impaired ability to synthesize DHA-Plasmalogen. The catch is that the supplement is expensive : A 3 month supply at list price is around $537.30 : Prodrome | ProdromeNeuro™ (Softgels) 180 Count. You can easily find a 25% off coupon and with more searching on the web you can find practitioners selling it up to 42% off. If you are already deficient you may need to increase the dosage for 1-3 months by 2x or 4x, so this solution can get quite expensive. They do have a $500 blood test that allows you to test if your body’s Plasmalogen levels (DHA-Plasmalogen as well as Omega9-Plasmalogen) are sufficient, so you can titrate your dosage to the lowest level required.

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Those prices are insane for a fancy Omega-3 supplement. For that price we could eat a jar of cold water fish caviar like it’s yogurt and still come out ahead (and likely get all the equivalent dose).